Antimicrobial Therapy Of Community-acquired Pneumonia Research Articles

Modern Directions of Optimization of Empirical Antimicrobial Therapy of Community-Acquired Pneumonia (Review)

Modern Directions of Optimization of Empirical Antimicrobial Therapy of Community-Acquired Pneumonia (Review)

Antimicrobial therapy of community-acquired pneumonia during stewardship efforts and a coronavirus pandemic: an observational study

BackgroundCommunity-acquired pneumonia (CAP) is the most frequent infection diagnosis in hospitals. Antimicrobial therapy for CAP is depicted in clinical practice guidelines, but adherence data and effect of antibiotic stewardship measures are lacking.MethodsA dedicated antibiotic team pointed out CAP as a potential target for antimicrobial stewardship (AMS) measures at a 1.000-bed, tertiary care, teaching university hospital in Norway from March until May for the years 2016 throughout 2021. The aim of the AMS program was to increase diagnostic and antimicrobial therapy adherence to national clinical practice guideline recommendations through multiple and continuous AMS efforts. Descriptive statistics were retrospectively used to delineate antimicrobial therapy for CAP. The primary outcomes were proportions that received narrow-spectrum beta-lactams, and broad-spectrum antimicrobial therapy.Results1.112 CAP episodes were identified. The annual proportion that received narrow-spectrum beta-lactams increased from 56.1 to 74.4% (p = 0.045). Correspondingly, the annual proportion that received broad-spectrum antimicrobial therapy decreased from 34.1 to 17.1% (p = 0.002). Trends were affected by the coronavirus pandemic. Mortality and 30-day readmission rates remained unchanged. De-escalation strategies were frequently unutilized, and overall therapy duration exceeded clinical practice guideline recommendations substantially. Microbiologically confirmed CAP episodes increased from 33.7 to 56.2% during the study period.ConclusionCAP is a suitable model condition that is sensitive to AMS measures. A continuous focus on improved microbiological diagnostics and antimicrobial therapy initiation is efficient in increasing adherence to guideline recommendations. There is an unmet need for better antimicrobial de-escalation strategies.

Effectiveness of antimicrobial therapy for community-acquired pneumonia in real clinical practice

Background. Community-acquired pneumonia (CAP) remains one of the most common infectious diseases, occupying an important place in the structure of mortality worldwide.Aim. To evaluate the effectiveness of antimicrobial therapy for community-acquired pneumonia in hospitalized patients in real clinical practice.Materials and methods. A retrospective, observational study was conducted, which included 236 patients hospitalized for community-acquired pneumonia at the Regional Clinical Hospital in Ryazan in 2019. Based on these case histories, an analysis of the effectiveness of the initial empiric antimicrobial therapy was performed.Results. The initial empiric antimicrobial therapy in 73% of cases included administration of ceftriaxone, in 45% of cases – levofloxacin, in 14% of cases – azithromycin. It was found that initial antimicrobial therapy was effective in 58% of patients who did not require replacement for the antibiotic. A need for a change in the treatment regimen was significantly associated with an increase in the length of hospitalization (p < 0.001), heart rate upon admission (p = 0.032), myelocyte count in the complete blood count (p < 0.001), and urea and blood creatinine levels (p = 0.004 and p = 0.044, respectively). The selected antimicrobial therapy regimen was significantly associated with the expected treatment effectiveness (p = 0.039). The choice of levofloxacin in monotherapy or in combination with ceftriaxone was accompanied by a decrease in the relative risk of replacing the antimicrobial, compared with other treatment regimens (odds ratio (OR) = 0.86 (95% confidence interval (CI): 0.55–1.34) and OR = 0.57 (95% CI: 0.37–0.87), respectively).Conclusion. Empiric antimicrobial therapy for community-acquired pneumonia in real clinical practice complies with current recommendations, however, at the same time, its ineffectiveness persists. Respiratory fluoroquinolones are most effective in treating pneumonia in hospitalized patients.

Current Issues of Empirical Therapy of Severe Bacterial Community-Acquired Pneumonia During the Season of Respiratory Viral Infections

Progredient growth of morbidity and mortality of patients with community-acquired pneumonia (CAP) requires optimization of treatment including antibacterial therapy. Implementation of molecular-genetic methods of diagnostics of viral and viral-bacterial infections in clinical practice has significantly augmented the conception of etiology of community-acquired pneumonia. Seasonal fluctuation of CAP prevalence corresponds with growth of morbidity of acute respiratory infections and influenza which contribute to the etiological structure of CAP by increasing the risk of infection caused by staphylococci. The synergy between influenza A virus and S.aureus has been shown; it is associated with an increase of virus replication in the presence of specific staphylococcal proteases and the ability of viruses to increase adhesion of S.aureusin the respiratory tract, to decrease phagocytosis of S.aureus by macrophages/neutrophils and production of antimicrobial peptides, as well as to increase the probability of secondary bacterial co-infection. Therefore, the most important requirement for the empiric therapy agents of CAP is high streptococcal and staphylococcal activity. According to the current guidelines on antimicrobial therapy of severe CAP, antipneumococcic cephalosporins, macrolides, and fluoroquinolones are the basic treatment agents, but none of them have the combined high antistaphylococcal and antipneumococcal activity inherent in ceftaroline. The advantages of ceftaroline over ceftriaxone and levofloxacin in terms of the probability of reaching target concentrations for clinically relevant pharmacokinetic/pharmacodynamic parameters are shown. Meta-analysis of randomized clinical trials showed the higher clinical efficacy of ceftaroline in comparison to ceftriaxone with similar adverse event rate. Summarized analysis of antibiotic susceptibility data, pharmacokinetic/pharmacodynamic and clinical data, as well as negative epidemiological trends confirms the necessity of optimization of antimicrobial therapy of CAP for implementation of ceftaroline advantages against pneumococci and staphylococci in comparison to other β-lactams. Therefore, empiric treatment with ceftaroline is the most rational option for the therapy of CAP in critically ill patients during the season of respiratory viral infection.

175. Impact of Infectious Diseases Pharmacist Interventions on Appropriateness of Antibiotics Prescribed at Hospital Discharge

BackgroundHospital discharge is an important opportunity for antimicrobial stewardship. Despite inpatient stewardship efforts, antibiotics ordered at discharge are frequently prescribed inappropriately. Discharge antibiotic therapy may be too broad or narrow in spectrum, inappropriately dosed, or for an unnecessarily long duration. The purpose of this study was to assess the inappropriateness of antimicrobial prescribing on discharge and to measure the effect of infectious diseases pharmacist (IDP) intervention on antibiotics prescribed at discharge from the inpatient setting.MethodsAnalyses were completed before and after implementation of an IDP intervention at hospital discharge. IDPs were alerted to patients discharged on antimicrobial therapy for community-acquired pneumonia (CAP), skin and soft tissue infections (SSTIs), and urinary tract infections (UTIs). IDPs reviewed patient and laboratory data and made recommendations for modifications of antibiotics prior to patients leaving the hospital. Prescribing algorithms were created and used to standardize the assessment of discharge antibiotics using local antibiograms and IDSA guidelines. The primary outcome was the composite of appropriateness including antibiotic dose, duration, and spectrum. Secondary outcomes included appropriateness of the individual components of the primary outcome as well as the mean total duration of antibiotic therapy per disease state.ResultsA total of 77 patients were assessed during the study period occurring December 2019 through February 2020. Intervention increased the rate of appropriate prescribing for the composite of antibiotic dose, duration, and spectrum from 48.1% at baseline to 84.4% (P < 0.05). By subset, intervention increased the proportion of patients receiving antibiotics of appropriate duration from 59.7% at baseline to 85.7% (P < 0.001), and proportion of patients receiving antibiotics of appropriate spectrum from 90.9% at baseline to 100% (P < 0.05). The mean duration of therapy for CAP decreased by 0.6 days (6.8 vs 7.4 days, P < 0.05).ConclusionIDP intervention improved appropriateness of prescribing consistent with guideline recommendations and local antibiogram data.Disclosures All Authors: No reported disclosures

2193. Factors Impacting the Duration of Antimicrobial Therapy for Community-Acquired Pneumonia

BackgroundPneumonia is a common cause of infection associated with hospitalization. Treatment durations for community-acquired pneumonia (CAP) often exceed guideline recommended durations of 5–7 days without a clear explanation. The objective of this study was to determine factors that may lead to durations exceeding this recommendation.MethodsA retrospective chart review of 89 patients admitted to the Detroit Medical Center (DMC) for the treatment of pneumonia was conducted. Demographics, clinical signs and symptoms, antibiotic data, pneumonia severity score (CURB 65), risk factors for resistance, microbiology results, and outcomes were recorded and analyzed for factors associated with increased durations of antibiotics. Average durations of antibiotics and durations of antibiotics greater that 7 days were assessed for each risk factor.ResultsAverage durations of antibiotics was 9 days (SD 3.8) for the cohort, and 55 (61%) received durations of > 7 days. Average durations of antibiotics for risk factors are shown in Table 1. Factors associated with durations of antibiotics longer than 7 days are shown in Table 2. There was a trend toward longer average durations of antibiotics for persons with risk factors for resistance [Drug Resistance in Pneumonia (DRIP) score ≥ 4 (increased duration of antibiotics by 1.7 days, P = 0.07] and those with a positive legionella antigen [increased durations of antibiotics by 6.6 days, P = 0.07].ConclusionSpecific risk factors could not be associated with increased durations of antibiotics, although there was a trend toward longer durations for persons with markers for resistance and positive legionella testing. Efforts to reduce durations of antibiotics must target global clinician antibiotic prescribing patterns and not specific risk factors. Disclosures All authors: No reported disclosures.

Pharmacoeconomic analysis of hospital antimicrobial therapy of community-acquired pneumonia using DDD and DU90% methods

This study was designed to compare results of pharmacoepidemiological analysis of antibacterial therapy in patients with community-acquired pneumonia (CAP) admitted to hospitals of Nizhniy Novgorod. Methods . Data for analysis were obtained from medical records of all patients with CAP (n = 117; 51.3% were males) admitted to two city hospitals in 2015 and 2016. Therapy of CAP was in agreement with corresponding standards. We analyzed real drug utilization using the defined daily dose (DDD) and drug utilization accounting for 90% of the total amount of DDD prescribed (DU90%). Results . Penicillinase-resistant penicillins, the 3rd generation cephalosporins and fluoroquinolones were the most often prescribed antibiotics in hospitals. The highest number of DDD was for ceftriaxone (376.0 g) in the hospital 1 and levofloxacin (468.16 g) in the hospital 2. The drugs constituting 90% of the prescription volume for inpatient therapy of CAP were ceftriaxone (46.09%), levofloxacin (20.0%), azythromycin (9.19%), and ciprofloxacin (9.19%) in the hospital 1 and ceftriaxone (16.50%), levofloxacin (71.19%), and ertapenem (4.70%) in the hospital 2. In the hospital 1, the cost of one DDD in DU10% segment (982.12 RUB) was 4-fold higher than that in DU90% segment (200.0 RUB); this suggests that inexpensive drugs were predominantly used in the hospital 1. In the hospital 2, DU10% consisted of two drugs accounting 24.56% of the total prescriptions. The cost of one DDD in DU90% segment (6 022.88 RUB) was 1.9-fold higher than that in DU10% segment (3 166.73 RUB); this suggests that more expensive antibiotics were widely used in the hospital 2. Conclusion . The strategy used in the hospital 2 is recommended according to the study results. The initial therapy with a single antibiotic could significantly reduce the drug load for the patient. Addition of the second antibiotic to the treatment was needed in 15% only, though patients were admitted to a hospital after the treatment failure both in ambulatory settings and in other hospitals.

Evaluating Duration of Antimicrobial Therapy for Community-Acquired Pneumonia in Clinically Stable Patients

Evaluating Duration of Antimicrobial Therapy for Community-Acquired Pneumonia in Clinically Stable Patients

Antimicrobial therapy of community-acquired pneumonia in a hospital setting (clinical and economic aspects)

The aim is to study the clinical and economic components of antimicrobial therapy (AMT) of community-acquired pneumonia (CAP) in a hospital ptactice. Materials and methods. Case reports of 48 patients with CAP hospitalized in FBU PMLC FMBA in the city of Nizhny Novgorod during 2016 were studied. All patients with CAP hospitalized during that period were included in the study. A retrospective analysis of AMT was carried out based on the data from inpatient CAP cases. Results. We compared the real number of prescriptions of antimicrobial agents for CAP in this hospital with the number of prescriptions required by the approved standards. We found that the real numbers exceeded the recommended standards in the cases of severe CAP as follows: 2.1- fold for 3d generation cephalosporins, 1.3-fold for fluoroquinolones, and 1.3-fold for carbapenems. Also notable was the use of ceftaroline fosamil – the 5th generation cephalosporin, which was not part of the standard therapy. Macrolides were not given to patients with severe CAP. In the treatment of CAP of moderate severity, fluoroquinolones were used 1.2 times more often than that recommended by the standard protocol, 3d generation cephalosporins – 1.5 times more often; macrolides – 5 times less often, as well as carbapenems (not part of the standard) and 5th generation cephalosporins (not part of the standard). The average duration and cost of monotherapy of moderate CAP were: 10.5 days and 731.65 rubles for ceftriaxone; 9.1 days and 1353.00 rubles – for levofloxacin; 4 days and 11035.36 rubles – for ceftaroline fosamyl; 9 days and 16,153.35 rubles – for ertapenem. Positive clinical outcomes were noted in 85% of cases. In 15% of cases, additional AMT was required. As a starting therapy for severe CAP, antimicrobial monotherapy was prescribed in 89.3% of cases. Its efficacy was 0.920. The treatment regimen was changed in two cases. Conclusion. The present findings, namely the discrepancy between the real number of AMT prescriptions and the standard recommendations might be due to an ineffective previous outpatient treatment and prolonged duration of the disease. It is important to note that the treatment standard was adopted in 2012. Since then, a number of novel effective AMT agents have been approved for clinical use: for example, ceftaroline fosamil – cephalos (cephalosporin of the 5th generation) is approved for the treatment of CAP, incl. in children from 2 months of age. There is also a change in the structure of the CAP pathogens that involves bacterial associations and the emergence of AMT resistant bacteria. The widespread use of macrolides inevitably leads to the development of new resistant strains. According to the published reports, the following species play an increasing role in the etiology of CAP: Streptococcus pneumoniae, Haemophilus influenzae, and also the associations S. pneumoniae-H. Influenzae and S. pneumoniae-M. pneumoniae. Associations of pathogens are observed in more than 60% of patients with CAP.

Analysis of the efficiency of antimicrobial treatment for community-acquired pneumonia in clinical practice

To analyze actual drug consumption based on the defined daily dose (DDD analysis) and to analyze the utilization of drugs based on their proportion of the total defined daily doses (DU90% analysis) for the antimicrobial therapy of community-acquired pneumonia (CAP) in clinical practice at a hospital in Russia. The investigation materials were the data of 117 case histories of male (51.3%) and female (48.7%) patients hospitalized with CAP at Nizhny Novgorod City Clinical Hospital Five in 2015. The investigation enrolled all the patients admitted to the hospital over the analyzed period. DDD analysis and DU90% analysis were used as study methods. DDD analysis and DU90% analysis of antimicrobial therapy for CAP were carried out at the hospital in clinical practice during a year. The annual number of defined daily doses (NDDD) for antimicrobial drugs, the number of defined daily doses per 100 bed-days (NDDD/100 bed-days), and a drug load (g) per 1000 CAP patients per day and per CAP patient per year were determined. The largest NDDD/year for CAP treatment with ceftriaxone was 376 g, or 43.43 NDDD/100 bed-days, which is much higher than that with other antimicrobial agents. The daily drug load of ceftriaxone per 1,000 CAP patients was 8.8 g, which exceeds that of moxifloxacin by 18.7 times, azithromycin and levofloxacin by 5 times, and ampicillin/sulbactam by 2.3 times. The daily drug load of ceftriaxone per CAP patient was 3.2 g, which exceeds that of of ampicillin/sulbactam by 2.3 times, levofloxacin and azithromycin by 5 times, and moxifloxacin by 19 times. It may be recommended that the proportion of cephalosporins as drugs that promote the rise of resistance in microbes and their production of extended-spectrum β-lactamases should be further limited, the proportion of penicillins be extended, and the administered ampicillin/sulbactam be added, for example, by amoxicillin/clavulanate. Penicillins contribute to the rise of resistance to a lesser degree, and the use of two different penicillin molecules specified in the guidelines for the treatment of CAP will be able to slow the process further. By the same reasoning, it is also advisable to use cefuroxime (second-generation cephalosporins) along with ceftriaxone in patients in stable condition, without impairing vital functions.

Antimicrobial Therapy for Pneumonia in the Emergency Department: The Impact of Clinical Pharmacists on Appropriateness.

IntroductionPneumonia impacts over four million people annually and is the leading cause of infectious disease-related hospitalization and mortality in the United States. Appropriate empiric antimicrobial therapy decreases hospital length of stay and improves mortality. The objective of our study was to test the hypothesis that the presence of an emergency medicine (EM) clinical pharmacist improves the timing and appropriateness of empiric antimicrobial therapy for community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP).MethodsThis was a retrospective observational cohort study of all emergency department (ED) patients presenting to a Midwest 60,000-visit academic ED from July 1, 2008, to March 1, 2016, who presented to the ED with pneumonia and received antimicrobial therapy. The treatment group consisted of patients who presented during the hours an EM pharmacist was present in the ED (Monday-Friday, 0900–1800). The control group included patients presenting during the hours when an EM clinical pharmacist was not physically present in the ED (Monday–Friday, 1800–0900, Saturday/Sunday 0000–2400 day). We defined appropriate empiric antimicrobial therapy using the Infectious Diseases Society of America consensus guidelines on the management of CAP, and management of HCAP.ResultsA total of 406 patients were included in the final analysis (103 treatment patients and 303 control patients). During the hours the EM pharmacist was present, patients were significantly more likely to receive appropriate empiric antimicrobial therapy (58.3% vs. 38.3%; p<0.001). Regardless of pneumonia type, patients seen while an EM pharmacist was present were significantly more likely to receive appropriate antimicrobial therapy (CAP, 77.7% vs. 52.9% p=0.008, HCAP, 47.7% vs. 28.8%, p=0.005). There were no significant differences in clinical outcomes.ConclusionThe presence of an EM clinical pharmacist significantly increases the likelihood of appropriate empiric antimicrobial therapy for patients presenting to the ED with pneumonia.

Evaluation of the Duration of Antimicrobial Therapy for Community-Acquired Pneumonia at a Large Academic Medical Center

Evaluation of the Duration of Antimicrobial Therapy for Community-Acquired Pneumonia at a Large Academic Medical Center

Антибиотикорезистентность штаммов Streptococcus pneumoniae, выделенных у госпитализированных пациентов с внебольничной пневмонией В РСО-Алания

An increase of antibiotic resistance of bacteria, in particular, Streptococcus pneumoniae, has been registered recently in most developed countries. This necessitates the study of regional characteristics of etiological structure of causative bacterial agents of community-acquired pneumonia and their sensitivity to antibiotics. The aim of the study was to study the spectrum of bacterial pathogens of community-acquired pneumonia and the sensitivity of Streptococcus pneumoniae to antimicrobial agents in hospitalized patients in the Republic of North Ossetia - Alania. Bacteriological examination of sputum with definition of sensitivity of isolated strains of bacteria to antibiotics was performed in 270 patients with community-acquired pneumonia. According to our data, the main causative agent of community-acquired pneumonia in hospitalized patients in the Republic of North Ossetia-Alania is Streptococcus pneumoniae. III generation cephalosporins, respiratory fluoroquinolones, macrolides, showed high activity against Streptococcus pneumoniae isolated from hospitalized patients. Low activity of natural and semi-synthetic penicillins was shown. The obtained results allow optimizing of antimicrobial therapy of community-acquired pneumonia caused by Streptococcus pneumoniae.

Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China.

Appropriate antimicrobial therapy of community-acquired pneumonia (CAP) is mainly based on the distribution of etiology and antimicrobial resistance of major pathogens. We performed a prospective observational study of adult with CAP in 36 hospitals in China. Etiological pathogens were isolated in each of the centers, and all of the isolated pathogens were sent to Zhongshan Hospital for antimicrobial susceptibility tests using agar dilution. A total of 593 patients were enrolled in this study, and 242 strains of bacteria were isolated from 225 patients. Streptococcus pneumoniae (79/242, 32.6%) was the most frequently isolated pathogen, followed by Haemophilus influenzae (55/242, 22.7%) and Klebsiella pneumoniae (25/242, 10.3%). Totally 527 patients underwent serological tests for atypical pathogens; Mycoplasma pneumoniae and Chlamydia pneumoniae infections were identified in 205 (38.9%) and 60 (11.4%) patients respectively. Legionella pneumophila infections were identified in 4.0% (13/324) of patients. The non-susceptibility rate of isolated Streptococcus pneumoniae to erythromycin and penicillin was 63.2% and 19.1% respectively. Six patients died from the disease, the 30-day mortality rate was 1.1% (6/533). The top three bacteria responsible for CAP in Chinese adults were Streptococcus pneumonia, Haemophilus influenza and Klebsiella pneumonia. There was also a high prevalence of atypical pathogens and mixed pathogens. The resistance rates of the major isolated pathogens were relatively low except for the high prevalence of macrolide resistance in Streptococcus pneumoniae.

Evolving trends in Streptococcus pneumoniae resistance: implications for therapy of community-acquired bacterial pneumonia

Pneumonia is a major infectious disease associated with significant morbidity, mortality and utilisation of healthcare resources. Streptococcus pneumoniae is the predominant pathogen in community-acquired pneumonia (CAP), accounting for 20–60% of bacterial cases. Emergence of multidrug-resistant S. pneumoniae has become a significant problem in the management of CAP. Although pneumococcal conjugate vaccine usage in children has led to significant decreases in morbidity and mortality due to S. pneumoniae in all age groups, disease management has been further complicated by the unexpected increase in resistant serotypes, such as 19A, in some regions. Until rapid and accurate diagnostic tests become available, initial treatment of CAP will remain empirical. Thus, selection of appropriate antimicrobial therapy for CAP must be based on prediction of the most likely pathogens and their local antimicrobial susceptibility patterns. This article reviews information on antimicrobial resistance patterns amongst S. pneumoniae and implications for managing CAP.

Empiric antimicrobial therapy of community-acquired pneumonia: Clinical diagnosis versus procalcitonin levels

Empiric antimicrobial therapy of community-acquired pneumonia: Clinical diagnosis versus procalcitonin levels

Measuring Acceptable Treatment Failure Rates for Community-Acquired Pneumonia: Potential for Reducing Duration of Treatment and Antimicrobial Resistance

This study was designed to establish the rates of treatment failure for community-acquired pneumonia that are acceptable to knowledgeable and experienced physicians, in order to facilitate the interpretation of existing studies and the design of new studies aimed at optimizing the duration of antibiotic therapy. Reducing the duration of antibiotic therapy is one strategy for reducing antibiotic exposure and thereby minimizing the potential for the emergence of antimicrobial resistance. Survey soliciting the acceptable failure rate for treatment given to an adult patient with uncomplicated community-acquired pneumonia treated with standard-of-care therapy in the outpatient setting. Analysis was performed using a modification of established methods of contingent valuation analysis. Six hundred eighty infectious diseases physicians in North America who were also members of the Emerging Infections Network of the Infectious Diseases Society of America. Three hundred seventy-five (55.1%) of 680 physicians responded to the survey. The median acceptable failure rate for treatment was 13.5%. Five hundred ten respondents (75.0%) found a failure rate of 7.3% acceptable, and 170 respondents (25.0%) found a failure rate of 19.8% acceptable. This study identified the failure rates for treatment of community-acquired pneumonia that were acceptable to infectious disease physicians. This range of acceptable treatment failure rates may facilitate the design of studies aimed at optimizing the duration of antimicrobial therapy for community-acquired pneumonia.

An Outbreak of Severe Clostridium difficile–Associated Disease Possibly Related to Inappropriate Antimicrobial Therapy for Community-Acquired Pneumonia

We report a severe outbreak of Clostridium difficile infection. According to a chart review, half of the patients who received treatment for bacterial pneumonia before they developed C. difficile infection may not have had pneumonia. Excessive use of the hospital's new pneumonia care plan during the influenza season may have contributed to the intensity of this outbreak.

Short-Course Therapy of Gemifloxacin Effective Against Pneumococcal Pneumonia in Mice

Standard 7-14 day (d) courses of antimicrobial therapy for community-acquired pneumonia (CAP) are thought to have contributed to the emergence of resistant pneumoccoci. Consequently, short-course fluoroquinolone regimens have been proposed to minimize resistance. To test this, we examined 2-day versus 5-day regimens of gemifloxacin and levofloxacin for treatment of pneumonia in a murine model. In doing so, we also investigated whether the enhanced potency of gemifloxacin would influence outcomes. CD1 Swiss mice were infected intratracheally with 105-CFU of a virulent Streptococcus pneumoniae strain. Drugs were administered every 8 h for 2 d and 5 d, starting at 24 h postinfection. Temperature was used to assess disease progression. Gemifloxacin remained effective for 2 d and 5 d, with survival rates of 100%-83% compared with 40%-58% for levofloxacin. Eighty-nine to 100% of gemifloxacin-treated mice were clear of pulmonary bacteria compared with only 0%-20% for levofloxacin. For levofloxacin-treated mice, 2 of 7 (29%) isolates with a levofloxacin minimum inhibitory concentration (MIC) 4 times that of the infecting parent strain had ParC mutations. By contrast, no isolates recovered from gemifloxacin-treated mice were reduced in susceptibility. Gemifloxacin could be effective in shortening duration of therapy for CAP treatment as well as minimize resistance development.

Short-Course Antimicrobial Therapy for Community-Acquired Pneumonia

Management of community-acquired pneumonia (CAP) remains surprisingly controversial. Optimal duration of antimicrobial therapy reflects one of the open questions due to the lack of sufficient randomized clinical trial data. Recently, there have been efforts to rationalize antimicrobial therapy of this disease. Trials addressing the issue of short-course antimicrobial therapy for CAP have revealed no adverse outcomes with a treatment duration of 5 days when compared with conventional courses of 7-10 days. There is accumulating evidence that a shorter duration of antimicrobial therapy may have benefits in patients with CAP, as it might enhance compliance, decrease the development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, reduce treatment costs and improve patient satisfaction with therapy. Nevertheless, remaining questions regarding the influence of patient selection, disease severity or choice of antimicrobial for short-course therapy indicate the need for further randomized controlled clinical trials in this area of research. This article summarizes current evidence for short-course therapy in patients with CAP and draws conclusions for clinical practice.